2026-04-29T07:35:49Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/270202025-12-18T12:57:34Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud author Nogales, Paula author Velasco, Carlos author González-Cintado, Leticia author Sharysh, Diana author Mota-Cobián, Adriana author Izquierdo-Serrano, Raúl author Torroja, Carlos author Del Rio-Aledo, David author Morales-Cano, Daniel author Mota, Rubén A author Benguría, Alberto author Dopazo, Ana author Sánchez-Cabo, Fátima author Vázquez, Jesús author España, Samuel author Carramolino, Laura author Mateo, Jesús author Bentzon, Jacob F funder Unión Europea. Comisión Europea. European Research Council (ERC) funder Instituto de Salud Carlos III funder Fundación La Caixa 2025-12-15T12:14:12Z 2025-12-15T12:14:12Z 2025-08-13 Sci Transl Med. 2025 Aug 13;17(811):eado6467. https://hdl.handle.net/20.500.12105/27020 40802740 SCIENCE TRANSLATIONAL MEDICINE Positron emission tomography (PET) imaging with the radiolabeled glucose analog fluorodeoxyglucose (FDG) is used to monitor atherosclerosis in clinical trials, but there is uncertainty regarding the plaque cell types that accumulate FDG and how uptake is regulated. The long-standing view that FDG is mainly taken up by macrophages is at odds with human and experimental data, and the impact of disease activity on FDG uptake has not been examined directly. To analyze the ability of FDG-PET to monitor disease activity, we developed a model of plaque regression in minipigs with hepatic overexpression of a gain-of-function mutant of (). Atherosclerosis was induced through 12 months of high-fat feeding in the porcine model. Disease activity was then lowered for 3 months by reducing plasma cholesterol with a low-fat diet alone or in combination with the microsomal transfer protein (MTP) inhibitor BMS-212122. Plaque regression in advanced lesions of the abdominal aorta was evident from reduced lipid content, reduced necrotic core size, and partial resolution of plaque inflammation and was accompanied by a decline in FDG-PET signal. Single-cell gene expression profiling revealed that plaque regression involved substantial down-regulation of genes encoding glycolytic enzymes in smooth muscle cells (SMCs), macrophages, and lymphocytes, which was corroborated by analysis of the plaque cellular proteome. These findings in a large-animal model suggest that FDG-PET can monitor atherosclerosis because of a close association between disease activity and glycolytic enzyme expression in all of the major plaque cell types. eng Atherosclerotic disease activity is associated with glycolytic enzyme expression across multiple cell types and is trackable by FDG-PET. research article 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 URL https://repisalud.isciii.es/bitstreams/910d2d24-9ed9-4ca4-8869-9c14d733772d/download File MD5 92c0e49d850175e6e0d6151318464815 3190295 application/pdf Atherosclerotic disease activity is associated_Sci Transl Med_2025.pdf